tbuckley/cabot-search huggingface dataset:
Educational inequalities in mortality and their mediators among generations across four decades: nationwide, population based, prospective cohort study based on the ChinaHEART project
Authors: Jiapeng Lu, Chaoqun Wu, Xiaoyan Zhang, Yang Yang, Jianlan Cui, Wei Xu, Lijuan Song, Hao Yang, Wenyan He, Yan Zhang, Jing Li, Xi Li
Journal: BMJ (2023)

To assess the different educational inequalities in mortality among generations born between 1940 and 1979 in China, and to investigate the role of socioeconomic, behavioural, and metabolic factors as potential contributors to the reduction of educational inequalities.Nationwide, population based, prospective cohort study.The ChinaHEART (China Health Evaluation And risk Reduction through nationwide Teamwork) project in all 31 provinces in the mainland of China.1 283 774 residents aged 35-75 years, divided into four separate cohorts born in 1940s, 1950s, 1960s, and 1970s.Relative index of inequality and all cause mortality.During a median follow-up of 3.5 years (interquartile range 2.1-4.7), 22 552 deaths were recorded. Among the four generations, lower education levels were found to be associated with a higher risk of all cause death: Compared with participants with college level education or above, the hazard ratio for people with primary school education and below was 1.4 (95% confidence interval 1.2 to 1.7) in the 1940s cohort, 1.8 (1.5 to 2.1) in the 1950s cohort, 2.0 (1.7 to 2.4) in the 1960s cohort, and 1.8 (1.4 to 2.4) in the 1970s cohort. Educational relative index of inequality in mortality increased from 2.1 (95% confidence interval 1.9 to 2.3) in the 1940s cohort to 2.6 (2.1 to 3.3) in the 1970s cohort. Overall, the mediation proportions were 37.5% (95% confidence interval 32.6% to 42.8%) for socioeconomic factors, 13.9% (12.0% to 16.0%) for behavioural factors, and 4.7% (3.7% to 5.8%) for metabolic factors. Except for socioeconomic measurements, the mediating effects by behavioural and metabolic factors decreased in younger generations.Educational inequalities in mortality increased over generations in China. Improving healthy lifestyles and metabolic risk control for less educated people, especially for younger generations, is essential to reduce health inequalities.
Potential for biosimilars in rheumatology in Africa
Authors: Mohamed Hassan Abu-Zaid, Adewale Adebajo, Yasser El Miedany
Journal: Annals of the Rheumatic Diseases (2023)

Biosimilars are products which are highly similar to a reference biologic product (RBP). In Africa, regulatory frameworks for biosimilar approval are still in development in many countries and few biosimilars for rheumatic diseases are currently available. The use of biosimilar medicines in Africa provides an important opportunity to treat more rheumatology patients with biologic drugs. This editorial aims to shed a light on the potential benefits, challenges and current efforts, regarding the use of biosimilars in Africa in Rheumatology.
Large-scale real-life analysis of survival and usage of therapies in multiple myeloma
Authors: N. Lopez-Muñoz, G. Hernández-Ibarburu, R. Alonso, J. M. Sanchez-Pina, R. Ayala, M. Calbacho, C. Cuellar, M. T. Cedena, A. Jiménez-Ubieto, R. Iñiguez, M. Pedrera, J. Cruz, L. Meloni, D. Pérez-Rey, P. Serrano, J. de la Cruz, J. Martinez-Lopez
Journal: Journal of Hematology & Oncology (2023)

Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.
Tailoring MSCs with modified mRNA for the eye
Authors: Joo Youn Oh
Journal: Molecular Therapy (2023)

Mesenchymal stem/stromal cells (MSCs) are among the most favored cell types in clinical trials. Over the past 25 years, more than 10,000 patients have received MSC infusions to treat various diseases. 1 Pittenger M.F. Discher D.E. Péault B.M. Phinney D.G. Hare J.M. Caplan A.I. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen. Med. 2019; 4: 22 Crossref PubMed Scopus (1012) Google Scholar The lessons learned so far from MSC clinical trials are that the safety profile of MSC-based therapies is excellent, but their therapeutic efficacy is inconsistent. The variability in the results of clinical trials is largely attributed to MSCs' molecular, cellular, and functional heterogeneity. 1 Pittenger M.F. Discher D.E. Péault B.M. Phinney D.G. Hare J.M. Caplan A.I. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen. Med. 2019; 4: 22 Crossref PubMed Scopus (1012) Google Scholar Ironically, however, it is this very functional heterogeneity that forms the basis for the broad therapeutic efficacy of MSCs as observed in a wide array of pre-clinical animal disease models, ranging from bone to eye. The pleiotropic effects of MSCs, including their anti-apoptotic, anti-inflammatory, anti-fibrotic, angiostatic, and neuroprotective properties, hold particular promise for treatment of corneal disease, wherein a complex interplay of multiple pathogenic mechanisms disrupts the immune and angiogenic privilege of the cornea, leading to formation of vision-impairing corneal scars. 2 Prockop D.J. Oh J.Y. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol. Ther. 2012; 20: 14-20 Abstract Full Text Full Text PDF PubMed Scopus (675) Google Scholar ,3 Oh J.Y. Lee R.H. Mesenchymal stromal cells for the treatment of ocular autoimmune diseases. Prog. Retin. Eye Res. 2021; 85100967 Crossref PubMed Scopus (18) Google Scholar Indeed, MSCs are currently being tested in multiple clinical trials for treatment of corneal disease. While awaiting the results of these trials, it is crucial to formulate strategies to overcome the challenges confronted in previous MSC trials and improve their outcomes. Given recent advances in the cell engineering toolkit, genetic modification of MSCs is one such strategy worth exploring. In this issue, Yu et al.4 Yu F. Gong D. Yan D. Wang H. Witman N. Lu Y. Fu W. Fu Y. Enhanced adipose-derived stem cells with IGF-1-modified mRNA promote wound healing following corneal injury. Mol. Ther. 2023; (S1525-0016(23)00258-7) Abstract Full Text Full Text PDF Scopus (4) Google Scholar provide compelling evidence that synthetic modified mRNA technology can be combined with MSC therapy to promote the therapeutic benefits of MSCs for the cornea and secure prolonged delivery of therapeutic proteins.
Discarded Targeted Oral Anticancer Medication—A Hard Pill to Swallow?
Authors: Cathy J. Bradley, K. Robin Yabroff, Ya-Chen Tina Shih
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Delivery of mutant huntingtin-lowering antisense oligonucleotides to the brain by intranasally administered apolipoprotein A-I nanodisks
Authors: Amirah E.-E. Aly, Nicholas S. Caron, Hailey Findlay Black, Mandi E. Schmidt, Christine Anderson, Seunghyun Ko, Helen J.E. Baddeley, Lisa Anderson, Lorenzo L. Casal, Reza S.M. Rahavi, Dale D.O. Martin, Michael R. Hayden
Journal: Journal of Controlled Release (2023)

Lowering mutant huntingtin (mHTT) in the central nervous system (CNS) using antisense oligonucleotides (ASOs) is a promising approach currently being evaluated in clinical trials for Huntington disease (HD). However, the therapeutic potential of ASOs in HD patients is limited by their inability to cross the blood-brain barrier (BBB). In non-human primates, intrathecal infusion of ASOs results in limited brain distribution, with higher ASO concentrations in superficial regions and lower concentrations in deeper regions, such as the basal ganglia. To address the need for improved delivery of ASOs to the brain, we are evaluating the therapeutic potential of apolipoprotein A-I nanodisks (apoA-I NDs) as novel delivery vehicles for mHTT-lowering ASOs to the CNS after intranasal administration. Here, we have demonstrated the ability of apoA-I nanodisks to bypass the BBB after intranasal delivery in the BACHD model of HD. Following intranasal administration of apoA-I NDs, apoA-I protein levels were elevated along the rostral-caudal brain axis, with highest levels in the most rostral brain regions including the olfactory bulb and frontal cortex. Double-label immunohistochemistry indicates that both the apoA-I and ASO deposit in neurons. Most importantly, a single intranasal dose of apoA-I ASO-NDs significantly reduces mHTT levels in the brain regions most affected in HD, namely the cortex and striatum. This approach represents a novel non-invasive means for improving delivery and brain distribution of oligonucleotide therapies and enhancing likelihood of efficacy. Improved ASO delivery to the brain has widespread application for treatment of many other CNS disorders.
FASDetect as a machine learning-based screening app for FASD in youth with ADHD
Authors: Lukas Ehrig, Ann-Christin Wagner, Heike Wolter, Christoph U. Correll, Olga Geisel, Stefan Konigorski
Journal: npj Digital Medicine (2023)

Abstract Fetal alcohol-spectrum disorder (FASD) is underdiagnosed and often misdiagnosed as attention-deficit/hyperactivity disorder (ADHD). Here, we develop a screening tool for FASD in youth with ADHD symptoms. To develop the prediction model, medical record data from a German University outpatient unit are assessed including 275 patients aged 0–19 years old with FASD with or without ADHD and 170 patients with ADHD without FASD aged 0–19 years old. We train 6 machine learning models based on 13 selected variables and evaluate their performance. Random forest models yield the best prediction models with a cross-validated AUC of 0.92 (95% confidence interval [0.84, 0.99]). Follow-up analyses indicate that a random forest model with 6 variables – body length and head circumference at birth, IQ, socially intrusive behaviour, poor memory and sleep disturbance – yields equivalent predictive accuracy. We implement the prediction model in a web-based app called FASDetect – a user-friendly, clinically scalable FASD risk calculator that is freely available at https://fasdetect.dhc-lab.hpi.de .
Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis
Authors: John P. Reilly, Zhiguo Zhao, Michael G. S. Shashaty, Tatsuki Koyama, Tiffanie K. Jones, Brian J. Anderson, Caroline A. Ittner, Thomas Dunn, Todd A. Miano, Oluwatosin Oniyide, John R. Balmes, Michael A. Matthay, Carolyn S. Calfee, Jason D. Christie, Nuala J. Meyer, Lorraine B. Ware
Journal: Intensive Care Medicine (2023)
From dengue outbreaks to endemicity: Reunion Island, France, 2018 to 2021
Authors: Muriel Vincent, Marie Claire Paty, Patrick Gerardin, Elsa Balleydier, Aurélie Etienne, Jamel Daoudi, Fabian Thouillot, Marie-Christine Jaffar-Bandjee, Luce Menudier
Journal: Eurosurveillance (2023)

Background After 40 years of limited viral circulation, Reunion Island has since 2018 experienced recurrent dengue outbreaks of increasing intensity and severity. Aim We aimed to report on the epidemiology and characteristics of dengue in Reunion Island between 2018 and 2021. Methods Between 2018 and August 2021, we systematically collected data on dengue cases via an automated transmission system between the health authorities and the medical laboratories. We set up additional surveillance systems for dengue-related activity in primary care, in emergency departments and in inpatient departments. Results Until 2020, despite numerous cases, outbreaks had a limited public health impact because of few severe cases, low lethality and no heavy burden for the health care system. In 2021, however, the number of severe cases increased (from 0.4% of all cases in 2018 to 0.8% in 2021), as did the number of paediatric cases (from 8% in 2018 to 15% in 2021) and atypical clinical forms of dengue (108 cases of post-dengue maculopathy). Of note, haemorrhagic forms were rare and multi-organ failure was the most frequent severity throughout the study period. In parallel, the dominant serotype switched from DENV2 to DENV1 in 2020 and DENV1 became the only serotype detected in 2021. Conclusion These findings indicate that dengue is becoming endemic in Reunion Island. Since comorbidities associated with severity of dengue are common in the population, health authorities should carefully consider the impact of dengue when addressing public health policies.
Practical Tracking Method based on Best Buddies Similarity
Authors: Haiyu He, Zhen Chen, Haikuo Liu, Xiangdong Liu, Youguang Guo, Jian Li
Journal: Cyborg and Bionic Systems (2023)

Visual tracking is a crucial skill for bionic robots to perceive the environment and control their movement. However, visual tracking is challenging when the target undergoes nonrigid deformation because of the perspective change from the camera mounted on the robot. In this paper, a real-time and scale-adaptive visual tracking method based on best buddies similarity (BBS) is presented, which is a state-of-the-art template matching method that can handle nonrigid deformation. The proposed method improves the original BBS in 4 aspects: (a) The caching scheme is optimized to reduce the computational overhead, (b) the effect of cluttered backgrounds on BBS is theoretically analyzed and a patch-based texture is introduced to enhance the robustness and accuracy, (c) the batch gradient descent algorithm is used to further speed up the method, and (d) a resample strategy is applied to enable the BBS to track the target in scale space. The proposed method on challenging real-world datasets is evaluated and its promising performance is demonstrated.
Liver mitochondrial cristae organizing protein MIC19 promotes energy expenditure and pedestrian locomotion by altering nucleotide metabolism
Authors: Jee Hyung Sohn, Beste Mutlu, Pedro Latorre-Muro, Jiaxin Liang, Christopher F. Bennett, Kfir Sharabi, Noa Kantorovich, Mark Jedrychowski, Steven P. Gygi, Alexander S. Banks, Pere Puigserver
Journal: Cell Metabolism (2023)
An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression
Authors: Qiong Luo, Yijun Liu, Ke Shi, Xuecheng Shen, Yaqi Yang, Xuejiao Liang, Liangliang Lu, Wenxuan Qiao, Airu Chen, Dongmei Hong, Yang Sun, Qiang Xu
Journal: Immunity (2023)
Excitatory neuron-specific suppression of the integrated stress response contributes to autism-related phenotypes in fragile X syndrome
Authors: Mehdi Hooshmandi, Vijendra Sharma, Carolina Thörn Perez, Rapita Sood, Konstanze Krimbacher, Calvin Wong, Kevin C. Lister, Alba Ureña Guzmán, Trevor D. Bartley, Cecilia Rocha, Gilles Maussion, Emma Nadler, Patricia Margarita Roque, Ilse Gantois, Jelena Popic, Maxime Lévesque, Randal J. Kaufman, Massimo Avoli, Elisenda Sanz, Karim Nader, Randi Jenssen Hagerman, Thomas M. Durcan, Mauro Costa-Mattioli, Masha Prager-Khoutorsky, Jean-Claude Lacaille, Veronica Martinez-Cerdeno, Jay R. Gibson, Kimberly M. Huber, Nahum Sonenberg, Christos G. Gkogkas, Arkady Khoutorsky
Journal: Neuron (2023)
Clostridioides difficile infection-associated cause-specific and all-cause mortality: a population-based cohort study
Authors: Annelies Boven, Erika Vlieghe, Lars Engstrand, Fredrik L. Andersson, Steven Callens, Johanna Simin, Nele Brusselaers
Journal: Clinical Microbiology and Infection (2023)

Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital- or community-acquired CDI, chronic comorbidities, and age.
Sphingosine-1-phosphate induces airway smooth muscle hyperresponsiveness and proliferation
Authors: Thomas J.A. Maguire, Stephanie Yung, Elena Ortiz-Zapater, O. Stephanie Kayode, Stephen Till, Chris Corrigan, Leonard Q.C. Siew, Gregory A. Knock, Grzegorz Woszczek
Journal: Journal of Allergy and Clinical Immunology (2023)

The emerging role of sphingosine-1-phosphate (S1P) in regulating smooth muscle functions has led to the exploration of the possibility that this sphingolipid could represent a potential therapeutic target in asthma and other lung diseases. Several studies in animal surrogates have suggested a role for S1P-mediated signaling in the regulation of airway smooth muscle (ASM) contraction, airway hyperresponsiveness, and airway remodeling, but evidence from human studies is lacking.We sought to compare the responsiveness of the airways to S1P in healthy and asthmatic individuals in vivo, in isolated human airways ex vivo, and in murine airways dissected from healthy and house dust mite (HDM)-sensitized animals.Airway responsiveness was measured by spirometry during inhalation challenges and by wire myography in airways isolated from human and mouse lungs. Thymidine incorporation and calcium mobilization assays were used to study human ASM cell responses.S1P did not induce contraction of airways isolated from healthy and HDM-exposed mice, nor in human airways. Similarly, there was no airway constriction observed in healthy and asthmatic subjects in response to increasing concentrations of inhaled S1P. However, a 30-minute exposure to S1P induced a significant concentration-dependent enhancement of airway reactivity to methacholine and to histamine in murine and human airways, respectively. HDM-sensitized mice demonstrated a significant increase in methacholine responsiveness, which was not further enhanced by S1P treatment. S1P also concentration-dependently enhanced proliferation of human ASM cells, an effect mediated through S1P receptor type 2, as shown by selective antagonism and S1P receptor type 2 small-interfering RNA knockdown.Our data suggest that S1P released locally into the airways may be involved in the regulation of ASM hyperresponsiveness and hyperplasia, defining a novel target for future therapies.
Primary Localized Conjunctival Amyloidosis: A Bilateral Presentation
Authors: Ricky Paramo, Anne Barmettler, Pooja Srivastava
Journal: Ophthalmology (2023)

A 62-year-old man presented with visually significant ptosis of the bilateral upper eyelids. Levator function was normal with no evidence of lagophthalmos. Lid eversion demonstrated bilateral soft, nontender, yellow-white masses on the upper palpebral conjunctiva (A-B). The remainder of the ocular examination was unremarkable. Intraoperative biopsies of both eyelids revealed the amorphous extracellular, eosinophilic deposition seen in amyloid, and confirmed with Congo red (C) and crystal violet staining (D). Systemic involvement was ruled out with a normal serum-free light chain ratio with negative serum electrophoresis. Primary localized conjunctival amyloidosis was diagnosed. Eyelid position improved after external levator advancement. (Magnified version of Figure A-D is available online at www.aaojournal.org).
GDF15 increases insulin action in the liver and adipose tissue via a β-adrenergic receptor-mediated mechanism
Authors: Kim A. Sjøberg, Casper M. Sigvardsen, Abdiel Alvarado-Diaz, Nicoline Resen Andersen, Mark Larance, Randy J. Seeley, Peter Schjerling, Jakob G. Knudsen, Georgios Katzilieris-Petras, Christoffer Clemmensen, Sebastian Beck Jørgensen, Katrien De Bock, Erik A. Richter
Journal: Cell Metabolism (2023)
Proceedings of the NHLBI Workshop on Artificial Intelligence in Cardiovascular Imaging
Authors: Damini Dey, Rima Arnaout, Sameer Antani, Aldo Badano, Louis Jacques, Huiqing Li, Tim Leiner, Edward Margerrison, Ravi Samala, Partho P. Sengupta, Sanjiv J. Shah, Piotr Slomka, Michelle C. Williams, W. Patricia Bandettini, Vandana Sachdev
Journal: JACC. Cardiovascular imaging (2023)
AI-powered therapeutic target discovery
Authors: Frank W. Pun, Ivan V. Ozerov, Alex Zhavoronkov
Journal: Trends in Pharmacological Sciences (2023)

Disease modeling and target identification are the most crucial initial steps in drug discovery, and influence the probability of success at every step of drug development. Traditional target identification is a time-consuming process that takes years to decades and usually starts in an academic setting. Given its advantages of analyzing large datasets and intricate biological networks, artificial intelligence (AI) is playing a growing role in modern drug target identification. We review recent advances in target discovery, focusing on breakthroughs in AI-driven therapeutic target exploration. We also discuss the importance of striking a balance between novelty and confidence in target selection. An increasing number of AI-identified targets are being validated through experiments and several AI-derived drugs are entering clinical trials; we highlight current limitations and potential pathways for moving forward.